{
  "abstract": "Introduction Vasoactive-vasodilating drugs (VVD) are the therapeutic cornerstone of pulmonary arterial hypertension (PAH), a form of precapillary pulmonary hypertension (pPH) that may complicate systemic sclerosis (SSc). VVD include endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5i), and prostanoids. As some VVDs are commonly used in SSc to treat digital ulcers (DU) and Raynaud’s phenomenon, we investigated the effectiveness of VVD on the primary prevention of SSc-pPH and, specifically, of PAH.Material and Methods SSc patients from the EUSTAR cohort who underwent right heart catheterization (RHC) were included; postcapillary PH cases were excluded. Multivariable logistic regression assessed the association between exposure to VVD (ongoing or ever; categories or specific molecules) and detection of pPH (mPAP>20 mmHg, PVR>2 WU and PWP<=15 mmHg) and of PAH (pPH, ILD extent <20% and FVC >70%). All models were adjusted for DLCO, age, current DU, sPAP on echocardiography, and interaction between VVDs and current DU.Results Among 944 eligible patients, 498 (53%) were diagnosed with pPH, of whom 367 (74%) had PAH. Patients with pPH were older, had more frequently anti-centromere antibodies, limited SSc, and had more frequently received ERAs and PDE5i. When testing VVD as categories in regression analysis, ERAs exposure was associated with a higher probability of pPH diagnosis. However, a significant interaction was found between these VVD and current digital ulcers (DU), which translated in a non-significant protective effect of ERAs exposure towards pPH detection in patients with current DU (ERAs ongoing: OR 0.435, 95%CI 0.193-1.064; ERAs ever: OR 0.636, 95%CI 0.349-1.158). No preventive effect was shown for ERAs in patients without current DU, as well as for PDE5i or prostanoids overall.When focusing on specific VVD molecules, a significant protective association with precapillary PH diagnosis was found for exposure ever to bosentan (OR 0.575, 95%CI 0.344-0.960), independently from current DU. Ongoing bosentan was associated with protective effects towards the diagnosis of pPH only in patients with current DU (OR 0.230, 95% CI 0.081 – 0.652), but not in those without DU. The protective effects of bosentan were confirmed in all sensitivity analyses targeting PAH detection.Conclusions Our data show that bosentan is associated with less frequent diagnosis of PAH and precapillary PH, in particular when employed in patients with current DU at the time of RHC. Our results support further research to optimize timing and patient selection for VVD therapy in SSc, aiming also at additional preventive effects at pulmonary level.",
  "authors": [
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy",
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy"
      ],
      "name": "Nicola Farina"
    },
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy"
      ],
      "name": "Silvia Bellando-Randone"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, Department of Internal Medicine and Clinical Immunology, Reference Center for Rare Autoi, Lille, France",
        "National Reference Center for Pulmonary Arterial Hypertension (Pulmotension), Lille, France"
      ],
      "name": "Sebastien Sanges"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Hospital of Southern Norway, Kristiansand, Norway"
      ],
      "name": "Hilde Jenssen Bjørkekjær"
    },
    {
      "affiliations": [
        "Department of Statistics, Informatics and Applications, University of Florence, Florence, Italy"
      ],
      "name": "Lorenzo Tofani"
    },
    {
      "affiliations": [
        "Rheumatology department, CHU de Bordeaux, Bordeaux, France"
      ],
      "name": "Marie-Elise Truchetet"
    },
    {
      "affiliations": [
        "University of Ghent, Department of Rheumatology, Ghent, Belgium"
      ],
      "name": "Vanessa Smith"
    },
    {
      "affiliations": [
        "Department of Rheumatology, St. Maria Hospital, Carol Davila, University of Medicine and Pharmacy, Bucarest, Romania"
      ],
      "name": "Andra Balanescu"
    },
    {
      "affiliations": [
        "Department Internal Medicine 3, University Hospital Erlangen, Erlangen, Germany"
      ],
      "name": "Christina Bergmann"
    },
    {
      "affiliations": [
        "Rheumatology Department, Université Paris Cité, Cochin Hospital, Paris, France"
      ],
      "name": "Yannick Allanore"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Clinical Immunology Center, JLU Giessen, Campus Kerckhoff, Bad Nauheim, Germany"
      ],
      "name": "Philipp Klemm"
    },
    {
      "affiliations": [
        "Reumatologia, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Rome, Italy"
      ],
      "name": "Simona Truglia"
    },
    {
      "affiliations": [
        "Section of Rheumatology, Department of Medicine, University of Verona, Verona, Italy"
      ],
      "name": "Luca Idolazzi"
    },
    {
      "affiliations": [
        "Centre for Rheumatology, Royal Free London and University College London Medical School, London, UK"
      ],
      "name": "Christopher Denton"
    },
    {
      "affiliations": [
        "Division of Rheumatology, A.O.U. Policlinico-San Marco, Catania, Italy"
      ],
      "name": "Roberta Foti"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Clinical Immunology, Geriatrics and Internal Medicine, Medical University of Gdansk, Univers, Gdansk, Poland"
      ],
      "name": "Anna Wojteczek"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Strasbourg, Strasburg, France"
      ],
      "name": "Emmanuel Chatelus"
    },
    {
      "affiliations": [
        "Department of rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands"
      ],
      "name": "Madelon Vonk"
    },
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy"
      ],
      "name": "Serena Guiducci"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, Department of Internal Medicine and Clinical Immunology, Reference Center for Rare Autoi, Lille, France",
        "National Reference Center for Pulmonary Arterial Hypertension (Pulmotension), Lille, France"
      ],
      "name": "David Launay"
    },
    {
      "affiliations": [
        "Univ. Lille, Inserm, CHU Lille, Department of Internal Medicine and Clinical Immunology, Reference Center for Rare Autoi, Lille, France",
        "National Reference Center for Pulmonary Arterial Hypertension (Pulmotension), Lille, France"
      ],
      "name": "Eric Hachulla"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Jeska de Vries-Bouwstra"
    },
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy"
      ],
      "name": "Anna Maria Hoffmann Vold"
    },
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy"
      ],
      "name": "Oliver Distler"
    },
    {
      "affiliations": [
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy"
      ],
      "name": "Marco Matucci-Cerinic"
    },
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy"
      ],
      "name": "Cosimo Bruni"
    }
  ],
  "title": "OC.10 Association between vasoactive-vasodilating therapy and reduced detection of pulmonary arterial hypertension in systemic sclerosis: evidence from a EUSTAR study",
  "uid": "8231fdb9-8429-5f14-bdf5-9acee7799f32"
}